Good morning everyone, while we're all waiting this week for news from the FDA on Gilead's sofosbuvir, LabCorp has captured our attention with a press release announcing the company's enhanced version of a drug resistance test used to screen for the Q80K polymorphism; a naturally occurring polymorphism that develops in certain strains of HCV, making the virus less susceptible to Janssen Therapeutics' OLYSIO(TM) (simeprevir),Quest Diagnostics also offers the Hepatitis C Viral RNA NS3 genotype test.

OLYSIO™ (simeprevir) - Q80K polymorphism
Last month, Olysio (simeprevir), the first "second wave direct-acting antiviral" was FDA approved in combination with peginterferon alfa and ribavirin to treat HCV genotype 1, adults, with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin. Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information.

In the QUEST-1 and QUEST-2
studies, researchers reported in QUEST-1 patients with HCV genotype 1a had almost
a 20% less SVR than HCV genotype 1b. As noted, at baseline, the mutation Q80K was
found in approximately 1/3 of genotype 1a patients. On the contrary, in QUEST-2
this mutation was infrequent and did not impact significantly the SVR rate.

Johnson & Johnson went on to perform an analysis pooling all
subjects from the C205, C206, C208, C216, and HPC3007 trials, and found 48
percent of U.S. patients with a HCV genotype 1a had the Q80K polymorphism at
baseline, compared to only 19 percent of patients in Europe. The mutation is
almost nonexistent in those with a genotype 1b infection.

**Notably, no Q80K-related reductions in
efficacy were observed during the pivotal trials of the currently approved
NS3/4A protease inhibitors, telaprevir and boceprevir.

Genotype 1a
treatment-naïve patients receiving OLYSIO who had the Q80K
polymorphismIn the QUEST-1 and
QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM
who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A
protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients
without the Q80K polymorphism. In the placebo arm, 52 percent of patients with
the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser
patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved
SVR12 versus 78 percent of patients without the polymorphism. In the placebo
arm, 30 percent of patients with the Q80K polymorphism achieved
SVR12.

Table 2 presents
SVR12 data by subgroups from the pooled studies in treatment-naïve subjects
(C208 and C216) as well as from the trial in subjects who relapsed after
prior interferon-based therapy (HPC3007). In all other subgroup
analyses presented in Table 2, SVR12 rates were significantly higher in the
simeprevir group compared to the Control group.

*A study of an all-oral combination of simeprevir
with Gilead's sofosbuvir has shown that the regimen mitigates the
effect Q80K has on simeprevir, Gaston Picchio, hepatitis disease area
leader at J&J's Janssen unit, said during the meeting.

As
mentioned, given the high frequency of the Q80K polymorphism in the
U.S. population and its significant negative impact on rates of
SVR12, according to the prescribing information, the FDA is
recommending that all Genotype 1a patients be screened for the Q80K
polymorphism. Alternative treatment options should be considered for
patients found to be infected with this polymorphic variant.

U.S. FDA Approves Gileads Harvoni (Ledipasvir/Sofosbuvir)
Harvoni is the first combination pill approved to treat chronic HCV genotype 1 infection. It is also the first approved regimen that does not require administration with interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection.

Both drugs in Harvoni interfere with the enzymes needed by HCV to multiply. Sofosbuvir is a previously approved HCV drug marketed under the brand name Sovaldi. Harvoni also contains a new drug called ledipasvir.Continue reading...

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Daclatasvir/VX-135..Vertex said it will license an experimental hepatitis C drug called VX-135 to Alios BioPharma..As a reminder (VX-135) is still on partial clinical hold by the FDA in the U.S. **Clinical Trials @ HCV Advocate-Vertex

How Soon Should I Get Tested After Exposure ?After the exposure (especially if the blood exposure involved another person known to have the hepatitis C virus), it is recommended that testing for the hepatitis C antibody be performed at 4 to 6 months after the exposure OR that testing for the hepatitis C virus itself (a test often called an HCV PCR or hepatitis C viral load test) be performed 4 to 6 weeks after the potential exposure. These tests are done to determine whether or not hepatitis C infection has occurred as a result of the exposure

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